The high incidence of Klebsiella infections in hospitals is compounded by the emergence of carbapenem-resistant organisms worldwide. Klebsiella pneumoniae is the most abundant carbapenem-resistant Enterobacteriaceae in the United States. Carbapenem-resistance is conferred largely by K. pneumoniae carbapenemase (KPC) or New Delhi metallo--lactamase 1 (NDM-1), either of which confers resistance to virtually all beta-lactam antibiotics. The most abundant strains in the United States produce KPC and are also resistant to fluoroquinolone and aminoglycoside antibiotics. These multidrug resistant strains are difficult to treat and there is a relatively high mortality rate associated with bacteremia. Although the vast majority of K. pneumoniae infections occur in hospitalized individuals, KPC is plasmid-encoded and has the potential to be readily exchanged among pathogens that cause community-associated infections, such as Escherichia coli. A K. pneumoniae lineage known as multi-locus sequence type 258 (ST258) is the most abundant lineage in the United States. Outside of carbapenem resistance, the molecular underpinnings of the emergence and success of this KPC lineage are incompletely determined, although considerable progress has been made.